Opiate receptors recognize endogenous opioid peptide neurotransmitters and exogenous opiate drugs of high abuse liability and analgesic benefits. Mu opiate receptors that recognize morphine with very high affinity are of particular interest. In order to improve understanding of these key elements in mediating opiate addictions, these workers have worked to clone opiate receptor CDNAS and thus elucidate structural and functional receptor features over this FY. Rat brain CDNAS whose predicted translation products display moderate identity with sequences of the recently-described delta-opiate receptor were identified through polymerase chain reaction and CDNA homology approaches. One CDNA recognizes a 10.5 kb MRNA that is expressed in thalamic neurons. COS cell expression confers naloxonazine-, NA+- and GTP-sensitive binding of mu, but not delta or k opioid ligands. Expressing cells bind morphine and other opioid peptide ligands with nanomolar or subnanomolar affinities, defining a mu opiate receptor that avidly recognizes analgesic and euphoric opiate drugs and opioid peptides.